This invention relates to a new class of antibiotics which may be generically represented by the following structural formula (I): ##STR1## wherein the dotted line indicates provision for both .DELTA..sup.2 and .DELTA..sup.3 embodiments; A is S, O, CH.sub.2, SO, or NR.sup.7 (R.sup.7 is selected from the group consisting of hydrogen, alkyl, formyl, acyl, thioacyl, alkylsulfonyl, and arylsulfonyl); X is OH, .dbd.O, SH, .dbd.NH, NH.sub.2, NHR.sup.7 ; R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen; substituted and unsubstituted: alkyl, aryl, aralkyl, heteroaryl and heteroaralkyl (mono- and bicyclic) wherein the heterocyclic moiety comprises 4-10 ring atoms and the hetero atom (for atoms) is O, N or S; wherein the ring or chain substituent is selected from amino, carboxy, hydroxy, alkoxy, carbalkoxy, lower alkyl, heteroaryl, and substituted amino such as mono- and dialkylamino, and acylamino, and perhaloalkyl; examples of such substituents, R.sup.1 and R.sup.2 are: methyl, trifluoromethyl, phenyl, substituted phenyl, benzyl and the like. R.sup.3 is selected from the group consisting of hydrogen, alkoxy, halogen, such as fluoro and bromo, and alkylthio; R.sup.6 is selected from the group consisting of PO(OH).sub.2, SO.sub.2 (OH), SO.sub.2 NH.sub.2 and derivatives thereof [see co-pending commonly assigned U.S. Patent Application Ser. No. 410,831 filed Nov. 8, 1973, now U.S. Pat. No. 4,032,521, incorporated herein by reference for definition of R.sup.6 ], and COXR.sup.8 wherein X is oxygen or sulphur and R.sup.8 is conventionally known in the cephalosporin and cephalosporin-like art and is, inter alia, representatively selected from the group consisting of hydrogen, trialkylsilyl, and the pharmaceutically acceptable salt, ester and amide moieties known in the art such as sodium, potassium, pivaloyloxymethyl, and the like; R.sup.5 is hydrogen, chloro, alkoxy, formyl or CH.sub.2 Y, wherein Y is hydrogen, hydroxy, halo, mercapto, acyloxy, acylthio, substituted hydroxy, substituted mercapto, a quaternary ammonium group, azido, amino or a N-substituted amino group.
There is a continuing need for new antibiotics. For unfortunately there is no static effectiveness of a given antibiotic because continued wide scale usage of any such antibiotic selectively gives rise to resistant strains of pathogens. In addition, the known antibiotics suffer from the disadvantage of being effective only against certain types of microorganisms--they are generally not effective against a broad range of pathogens.
Unexpectedly, it has been found that the compounds of the present invention are broad spectrum antibiotics, which are useful in animal and human therapy and in inanimate systems. It will be recognized from the above generic representation (I) that the principal novel feature of the compounds of the present invention is the 7-substituted methyl substituent, which position heretofore in the cephalosporin art has always been amino or substituted amino for compounds of high activity. It will also be noted, except where expressly stated, that the balance of the cephalosporin or cephalosporin-like structure (I) is well-known in the relevant art.
Thus, it is an object of the present invention to provide a novel class of antibiotics which inclues, inter alia, species having the basic nuclear structure of the cephalosporins but which are characterized by having a substituted methyl substituent at the 7-position of the .beta.-lactam ring. These antibiotics are active against a broad range of pathogens which representatively include both gram positive bacteria such as Staphylococcus aureus and Streptococcus pyrogenes and gram negative bacteria such as E. coli and Klebsiella pneumoniae. Further objects of this invention are to provide chemical processes for the preparation of such antibiotics; pharmaceutical compositions comprising such antibiotics; and to provide methods of treatment comprising administering such antibiotics and composition when an antibiotic effect is indicated.